Described are dual mass-spectrometry-cleavable cross-linkers that can be cleaved selectively using two differential tandem mass-spectrometric techniques such as collision induced dissociation (CID) or electron transfer dissociation (ETD), i.e., a dual cleavable crosslinking technology (DUCCT) cross-linker. When used to cross-link a macromolecule, such as a peptide, MS/MS fragmentation produces two signature complementary mass spectra of same cross-linked peptides, the analysis of which gives rise to high confidence in characterizing the structures of the cross-linked macromolecules as well as sites of interactions. Also described, are methods of making and using DUCCT cross-linkers.

Disclosed herein, inter alia, are methods of use and composition of novel inhibitors that target the Smac binding site of a variety of inhibitor of apoptosis proteins that contain a Bir domain, including XIAP, cIAP1, cIAP2, or other IAP proteins.

Described are dual mass-spectrometry-cleavable cross-linkers that can be cleaved selectively using two differential tandem mass-spectrometric techniques such as collision induced dissociation (CID) or electron transfer dissociation (ETD), i.e., a dual cleavable crosslinking technology (DUCCT) cross-linker. When used to cross-link a macromolecule, such as a peptide, MS/MS fragmentation produces two signature complementary mass spectra of same cross-linked peptides, the analysis of which gives rise to high confidence in characterizing the structures of the cross-linked macromolecules as well as sites of interactions. Also described, are methods of making and using DUCCT cross-linkers.

The invention is directed to the use of at least one peptide of formula: X-(Xaa.sub.1).sub.n-Pro*-(Xaa.sub.2).sub.m-Y (I) With: -n=0, 1 or 2; -m=0 or 1 and if m=0 then n0 -Xaa.sub.1 is: -An hydrophobic aminoacid selected from Alanine (Ala, A), Valine (Val, V), Methionine (Met, M), Leucine (Leu, L), Isoleucine (Ile, I), Phenylalanine (Phe, F), Proline (Pro, P) and analogues and derivatives thereof; -A polar aminoacid selected from Serine (Ser, S), Threonine (Thr, T), Tyrosine (Tyr, Y), Asparagine (Asn, N), Glutamine (Gln, Q) and analogues and derivatives thereof; -or Glycine (Gly, G); When n=2 the two aminoacids Xaa.sub.1 can be the same or different; -Xaa.sub.2 is: -An hydrophobic aminoacid selected from Alanine (Ala, A), Valine (Val, V), Methionine (Met, M), Leucine (Leu, L), Isoleucine (Ile, I), Phenylalanine (Phe, F), Proline (Pro, P) and analogues and derivatives thereof; -A basic aminoacid selected from Arginine (Arg, R), Lysine (Lys, K) and Histidine (His, H) and analogues and derivatives thereof; -Glycine (Gly, G) or Serine (Ser, S); -At the N terminal end of the peptide, X is selected from H, COR.sub.1 and SO.sub.2R.sub.1; -At the C terminal end of the peptide, Y is selected from OH, OR.sub.1, NH.sub.2, NHR.sub.1 or NR.sub.1R.sub.2, R.sub.1 and R.sub.2 being independently from each other, selected from an alkyle, aryle, aralkyle, alkylaryl, alkoxy and aryloxy group, that can be linear, branched, cyclic, poly-cyclic, non-saturated, hydroxylated, carbonylated, phosphorylated and/or sulphured, with the possibility to have in said group skeleton a O, S and/or N heteroatom; -Pro* corresponding to a Proline, an analogue or derivative thereof; Excluding the peptides where X=H and Y=OH, for a non therapeutical cosmetic pro-pigmenting treatment of skin. The invention also encompasses new tripeptides of formula (I) suitable for a non therapeutical cosmetic treatment of skin.

The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepine compounds of formula (I)-(VI). The invention also provides conjugates of the benzodiazepine compounds linked to a cell-binding agent. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention.

Provided are modified lipid compounds and their use in the formation of lipid assemblies. Also provided are lipid assemblies including (a) an amphoteric lipid including in covalent association with (i) one or more acyl chains; (ii) one or more weak base moiety; (iii) one or more weak acid moiety; the lipid assembly also including (b) one or more additional lipids, at least one of which being a zwitterionic lipid. In some embodiments, the amphoteric lipid is a compound including (a) a tri-functional moiety; (b) two non-phosphate lipid chains associated with two of the functional moieties of said tri-functional moiety; (c) optionally a spacer moiety associated with the third of the functional moieties of said tri-functional moiety; and (d) a polyalkylamine optionally including a short peptide with one to several carboxylic acid residues. Further provided are the uses of the lipid assembly, inter alia, for transfection or cancer treatment.

Novel compounds and methods for the inhibition of biological barrier permeability and for the inhibition of peptide translocation across biological barriers are identified. Assays for determining modulators of biological barrier permeability and for peptide translocation across biological barriers are provided. Methods for treating diseases relating to aberrant biological barrier permeability and peptide translocation across biological barriers are provided. Such diseases include celiac disease, necrotizing enterocolitis, diabetes, cancer, inflammatory bowel diseases, asthma, COPD, excessive or undesirable immune response, gluten sensitivity, gluten allergy, food allergy, rheumatoid arthritis, multiple sclerosis, immune-mediated or type 1 diabetes mellitus, systemic lupus erythematosus, psoriasis, scleroderma and autoimmune thyroid diseases.

A novel substance which adds body to a food product, and a body-adding agent for food products that uses said substance are provided. More specifically, the body adding agent for food products is characterized by having as an active component a peptide, or a salt thereof, that is characterized in that the -glutamyl bond number is 2-4 and the peptide chain length is the -glutamyl bond number +1 to +2, a food product manufacturing method that uses said peptide, and a method for adding body to a food product, characterized by adding said peptide are provided.

Charged or pro-charged cross-linking moieties and conjugates of cell binding agents and drugs comprising the charged or pro-charged cross-linking moieties and method of making the same.

The present application discloses a crystal of oxidized glutathione dication salt and a method of producing the same.